Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man

作者：Barnes Eleanor; Folgori Antonella; Capone Stefania; Swadling Leo; Aston Stephen; Kurioka Ayako; Meyer Joel; Huddart Rachel; Smith Kira; Townsend Rachel; Brown Anthony; Antrobus Richard; Ammendola Virginia; Naddeo Mariarosaria; O' Hara Geraldine; Willberg Chris; Harrison Abby; Grazioli Fabiana; Esposito Maria Luisa; Siani Loredana; Traboni Cinzia; Oo Ye; Adams David; Hill Adrian; Colloca Stefano; Nicosia Alfredo; Cortese Riccardo; Klenerman Paul^*

来源：Science Translational Medicine, 2012, 4(115): 115ra1.

DOI：10.1126/scitranslmed.3003155

Currently, no vaccine exists for hepatitis C virus (HCV), a major pathogen thought to infect 170 million people globally. Many studies suggest that host T cell responses are critical for spontaneous resolution of disease, and preclinical studies have indicated a requirement for T cells in protection against challenge. We aimed to elicit HCV-specific T cells with the potential for protection using a recombinant adenoviral vector strategy in a phase 1 study of healthy human volunteers. Two adenoviral vectors expressing NS proteins from HCV genotype 1B were constructed based on rare serotypes [human adenovirus 6 (Ad6) and chimpanzee adenovirus 3 (ChAd3)]. Both vectors primed T cell responses against HCV proteins; these T cell responses targeted multiple proteins and were capable of recognizing heterologous strains (genotypes 1A and 3A). HCV-specific T cells consisted of both CD4(+) and CD8(+) T cell subsets; secreted interleukin-2, interferon-gamma, and tumor necrosis factor-alpha; and could be sustained for at least a year after boosting with the heterologous adenoviral vector. Studies using major histocompatibility complex peptide tetramers revealed long-lived central and effector memory pools that retained polyfunctionality and proliferative capacity. These data indicate that an adenoviral vector strategy can induce sustained T cell responses of a magnitude and quality associated with protective immunity and open the way for studies of prophylactic and therapeutic vaccines for HCV.

• 出版日期2012-1-4